Career Enhancement for Epigenetic Research on Substance Abuse and Comorbidities This application addresses the call for further progress on the epigenetic agenda which requires a shift from a multidisciplinary approach (experts in scientific fields bringing disciplinary insights) to an interdisciplinary approach (disciplinary-based scientists sharing a basic understanding of each other's language, theories, methods of data collection and analytic techniques). The proposed activities will foster greater synergy and bring a complex approach to the conceptualization and conduct of research on the epigenetics of substance use disorders (SUDs) and their comorbidity with serious mental illness (SMIs). Two specific aims are designed to: 1) Engage in a short-term, intense training plan to better integrate the centrality and presence of basic behavioral and social science research (b-BSSR) on an interdisciplinary team focused on the onset of SUDs and their comorbidity with SMIs by increasing knowledge of biomedical research (BMR) theories, tools, methods of data collection, and analytic techniques. This includes 1.a.) Improve understanding of basic and behavioral genetics, physiology, and neuroscience through a series of face-to-face and electronic courses over a 12 month period;and 1.b) Improve knowledge of research ethics targeted to the unique issues that arise in research on genetics and epigenetics relevant to SUDSs and their comorbidity with SMIs;2) Develop and carry out a research project that brings b-BSSR theories and analytic approaches into an established research program focusing on genetic and epigenetic analyses of one of the premier BMR data programs, the Collaborative Study of the Genetics of Alcoholism (COGA, N= 10,646 probands, families and controls). More specifically, 2.a.) Reconceptualize and empirically examine current epigenetic models of SUDs, including polyuse and comorbidity problems as representing differential pathways by which b-BSSR theories of illness interact with (or work through) each other, candidate genes and gene clusters. Building on the base of an initial productive, multidisciplinary collaboration, this application, with Bernice A. Pescosolido (Distinguished Professor of Sociology) as PI/Candidate and John Nurnberger, Jr. (Joyce and Iver Small Professor of Psychiatry and Professor of Medical and Molecular Genetics) as Mentor, requests one year of protected time designed to achieve a shift in the focus of research. This will be accomplished in part through additional training that will enrich a current research program designed to improve interdisciplinary collaborations on issues of SUDs and comorbidity by enhancing the ability of b-BSSR scientists to integrate tools and approaches from other related science areas. PUBLIC HEALTH RELEVANCE: The complex causes of substance abuse disorders, including the use of multiple substances (polyuse) and co- occurrence with mental health problems (comorbidity) require scientists from both the biomedical and social sciences to pool their expertise to understand and offer solutions. Building on an initial, productive collaboration between a sociologist and a medical/molecular geneticist, this project provides opportunities for targeted training and research to facilitate a research agenda focused on how the social environment triggers, suppresses or otherwise is involved in genetic predispositions to substance abuse and comorbidity.